INTRODUCTION:

The Punica granatum, also known as the Pomegranate, is a tiny tree that grows to a height of five to eight meters. It is mostly found in Iran, China, the USA, the Himalayas in northern India, and the Mediterranean region. For many years, the Pg fruit has served as a traditional treatment for respiratory disorders, haemorrhage, helminth infection, acidosis, diarrhoea, and microbiological diseases¹. Recently, individuals have demonstrated a significant deal of interest in pomegranates due to reports of its health benefits. The pomegranate is now used in many different forms as a functional food ingredient and dietary supplement, including fresh fruit and juice, powdered capsules and tablets containing extracts of various pomegranate tissues, tea made from pomegranate leaves, jam, jelly, juice and wine made from pomegranate fruits, and spices made from dried seeds². The bioactive ingredients in pomegranates that are consumed include lignans, proanthocyanidins, anthocyanins, anthocyanidins, flavonoids, vitamins, sterols, saccharides, fatty acids, organic acids, terpenes, and terpenoids. Proanthocyanidins, in particular, were studied with an emphasis on their effects on systemic lipid-lowering, intestinal epithelium hypoglycaemia, and anti-inflammatory properties³. Proanthocyanidins have a noteworthy effect on human health. Strong antioxidants including flavonoids, tannins, and anthocyanins found in pomegranates aid in lowering the body's level of oxidative stress⁴. Chronic inflammation is associated with insulin resistance and the development of diabetes. According to some research, pomegranate extract may increase insulin sensitivity, which would help people with diabetes or prediabetes better regulate their blood sugar levels⁵. It has been grown and assimilated throughout the Mediterranean region from ancient times, despite its cultivation beginning in the northern Indian Himalayas. This includes Iran. While pomegranates are known for their general health benefits, there hasn't been much comparison of the various varieties based on their bioactive components and bioactivity in the scientific community⁶. In addition to identifying the most bioactive types of pomegranates and outlining possible ingestion paths, this study aims to fill in current knowledge gaps and provide a broad, well-organized overview of the body of information on pomegranates⁷.

1. Pomegranate Composition and Active Constituents:

Pomegranate fruits have many different ingredients in their seeds, skins, and arils, to name a few. The peel of the pomegranate, which comprises around 60% of the fruit, is rich in flavonoids, ellagitannins, and proanthocyanidin compounds, as well as minerals including calcium, magnesium, phosphorus, potassium, and salt. Pomegranate juice's 15% dry matter is made up of sugars, pectins, organic acids, vitamins, and minerals ⁸. Antioxidant polyphenols such as hydrolysable tannins, condensed tannins, anthocyanins, flavonols, and phenolic acids are abundant in the juice. Hydrolysable tannins, condensed tannins, flavonols, anthocyanins, phenolic and organic acids, and flavonols have all been demonstrated to provide a variety of health benefits against ailments⁹. Punicic acid, linoleic acid, and oleic acid are the three fatty acids that are most common in pomegranate seed oil. Punicic acid, a conjugated fatty acid with three double bonds and eight carbons, makes up around 80% of the oil in pomegranate seeds. Punicic acid ranged from 73.4% to 83.5% of total fatty acids, according to the report. On the other hand, 7% of pomegranate seed oil is composed of linoleic acid, with other less frequent ingredients including sterols, tocopherols, and cerebrosides¹⁰.

2. Occurrence and Structure of Diverse Phytochemicals in Pomegranate:

Pomegranate (Punica granatum) is renowned for its rich content of diverse phytochemicals, which contribute to its health-promoting properties. Here's an overview of some of the key phytochemicals found in pomegranate and their structures:

3.1 Ellagic Acid: Ellagic acid is a polyphenolic compound abundant in pomegranate. It's a dimer of gallic acid and forms complex structures with glucose molecules known as ellagitannins¹¹.

Figure no.2: Chemical structure of Ellagic acid

3.2 Punicalagins: Another class of polyphenolic chemicals present in pomegranate peel and juice at high concentrations is punicalagins. Punicalagins are made up of many gallic acid units esterified to a glucose molecule¹².

Figure no. 3: Chemical structure of Punicalagins

3.3 Anthocyanins: Anthocyanins, which give pomegranate arils their vivid red color, are found in them. These pigments are soluble in water and are classified as flavonoids. Their structures vary. Delphinidin, cyanidin, and derivatives of pelargonidin are a few examples ¹³.

Figure no. 4: Chemical structure of Anthocyanins

3.4 Flavonols: Flavonols including myricetin, kaempferol, and quercetin are found in pomegranates. These substances have anti-inflammatory, anti-diabetic, and antioxidant qualities^14,15.

Figure no. 5: Chemical structure of Flavonols

Figure no.6: The natural compounds of Pomegranate

4. Biological Activities Relevant to Diabetes Management:

Figure no.7: Pomegranates are rich in phytoconstituents which show numerous beneficial health properties

4.1 Antioxidant Properties:

Antioxidants abound in pomegranates, especially polyphenols such flavonoids, ellagic acid, and punicalagins. Previous research has demonstrated that leaves and peels have extremely strong antioxidant activity, and that extracts from seeds have varied degrees of antioxidant activity, with sour white peel exhibiting the highest potency¹⁶.

4.2 Anti-inflammatory Effects:

Pharmacokinetic investigations demonstrated the potent anti-inflammatory qualities of the flavonoids procyanidin, which is present in the juice, kaempferol and luteolin in the peel. The standardized pomegranate rind extract's topical anti-inflammatory and analgesic effects were evaluated, and the results showed that both the rind extract and the corresponding ellagic acid (EA) reduced the ear edema in a dose-dependent manner¹⁷.

4.3 Anti-Diabetic Activity:

An ethanolic leaf extract was discovered to exhibit significant anti-diabetic properties and to be very successful in treating the difficulties arising from diabetes mellitus. As a result, the concentrations of glucose, triglycerides, cholesterol, and LDL cholesterol decreased while the amount of haemoglobin and HDL cholesterol increased. The study's findings demonstrated that rind and seed extracts considerably reduced the rise in blood glucose^18,19.

4.4 Cardio-Vascular Effect:

In the US, cardiovascular disease is the leading cause of mortality and disability. Thirteen Atherosclerosis is a disorder that causes the endothelium lining of medium- to large-sized arteries to accumulate fatty deposits or atherosclerotic plaques, which reduces or obstructs blood flow. The main cause of the recurrent, mild damage to the endothelial cells lining the arterial walls through a variety of pathways is multiplicative atherosclerosis²⁰.

4.5 Lipid-Lowering Effect:

Studies have demonstrated that pomegranate extracts can reduce the build-up of lipids in a number of tissues, including the skeletal muscles and liver. Based on multiple research, pomegranate juice consumption may lower LDL (bad) cholesterol levels. LDL cholesterol is one of the primary risk factors for cardiovascular disease²¹.

4.6 Modulation of Gut Microbiota:

Prebiotic substances found in pomegranates include fibres like pectin and polyphenols like ellagitannins. Prebiotics are substances that promote the development and activity of two beneficial bacterial species in the stomach: Lactobacilli and Bifidobacteria. A balanced and diversified gut flora has been linked to better immune system function, improved digestion, and possibly a decreased chance of acquiring certain disorders like obesity, diabetes, and inflammatory bowel disease (IBD). These health benefits may be connected to the pomegranate's beneficial effects on gut bacteria^22,23.

4.7 Antitumor Activity:

The substances that were investigated the most were anthocyanins, luteolin, punicic acid, and ellagic acid. Prostate cancer cell lines from rats (PLS10) and humans (PC-3) that are androgen-independent have shown that elaginic acid is effective at preventing cell motility and invasion. It was discovered in a recent study that punicic acid, luteolin, and ellagic acid inhibit the CXCL12/CXCR4 axis, which is necessary for metastasis and the growth of PC-3M-luc primary tumors²⁴.

5. Mechanisms of Action in Diabetes Management:

An adult human's gut is home to over 100 trillion microorganisms. Commensal bacteria produce vitamins, break down lipids and cholesterol, strengthen the immune system of the host, guard against dietary allergies and cancer, and enhance mineral absorption. Additionally, they confer disease resistance to the host during colonization. Pomegranate byproducts and punicalagins limit the growth of several pathogenic Clostridia species, Staphylococcus aureus, and Pseudomonas aeruginosa, but they promote the production of short-chain fatty acids and the growth of Bifidobacterium infantis and Bifidobacterium breve. The primary regulators of lipid and glucose metabolism are PPARs. PPARs have the ability to control metabolism, immunity, and inflammation²⁵.

6. Potential Application of Pomegranate in Diabetes:

Because pomegranate fruit has so many seeds, it is associated with fertility, birth, and everlasting life. PJ significantly reduced the amount of malondialdehyde (MDA). Rats given varying dosages of PJ also showed a significant rise in vitamin C levels, catalase (CAT) activities, glutathione (GSH), and glutathione peroxidase (GSH-Px). Eating PJs increased the concentration of epididymal sperm, spermatogenic cell density, diameter of the seminiferous tubules, sperm motility, and thickness of the germinal cell layer²⁶. The effects of pomegranate flower (PGF), a traditional anti-diabetic medication, on fatty liver and its underlying mechanism have been studied. The results imply that this Unani medication, at least in part, improves fatty liver linked to diabetes and obesity by triggering the expression of fatty acid oxidation-related genes in the liver. Consuming pomegranate fruit decreased the composite Disease Activity Index (DAS28) in individuals with rheumatoid arthritis; this effect may be attributed to pomegranates' antioxidant qualities. Pomegranate dietary supplements may be a helpful adjunctive method for reducing rheumatoid arthritis patients' clinical symptoms^27,28.

7. CONCLUSION:

Traditional herbal medicine has utilized pomegranate fruits, leaves, blossoms, and seeds to treat a variety of ailments. But the bioactive metabolites in pomegranate fruit peel and juice have received a lot more attention than those in other tissues. The ET derivatives urolithins have shown numerous health benefits in animal model studies and in vitro investigations. It is essential to have clinically significant data on their efficacy prior to their widespread use in human illness treatment. Preclinical and clinical studies of the bioactivities of pomegranate phytochemicals, along with more study into their diversity and interactions, seem very promising in order to fully realize the promise of this ancient fruit and modern functional food.

8. REFERENCES:

1. Facciola S. Cornucopia: a Source Book of Edible Plants. Vista, California: Kampong Publications; 1990. p. 166.

2. Kim YH, Choi EM. Stimulation of osteoblastic differentiation and inhibition of interleukin-6 and nitric oxide in MC3T3-E1 cells by pomegranate ethanol extract. Phytother. Res. 2009; 23:737–739.

3. Fahmy HA, Farag MA. Ongoing and potential novel trends of pomegranate fruit peel; a comprehensive review of its health benefits and future perspectives as nutraceutical. Journal of Food Biochemistry. 2022 Jan;46(1): e14024.

4. 4.F. Boussaa, F. Zaouay, F. Burlo-Carbonell, L. Noguera-Artiaga, A. Carbonell-Barrachina, P. Melgarejo, F. Hernandez, M. Mars

5. Mannino G, Chinigò G, Serio G, Genova T, Gentile C, Munaron L, Bertea CM. Proanthocyanidins and where to find them: A meta-analytic approach to investigate their chemistry, biosynthesis, distribution, and effect on human health. Antioxidants. 2021 Jul 30;10(8):1229.

6. Banihani S, Swedan S, Alguraan Z. Pomegranate and type 2 diabetes. Nutrition research. 2013 May 1;33(5):341-8.

7. O'Grady L. Effects of postharvest handling on nutritional quality of pomegranate (Punica granatum) Arils (Doctoral dissertation, Stellenbosch: Stellenbosch University).

8. Hotel B, Petra-Jordan R. The 3 rd International Symposium on Medicinal Plants, Their Cultivation and Aspects of Uses.

9. Melgarejo-Sánchez P, Núñez-Gómez D, Martínez-Nicolás JJ, Hernández F, Legua P, Melgarejo P. Pomegranate variety and pomegranate plant part, relevance from bioactive point of view: A review. Bioresources and Bioprocessing. 2021 Dec; 8:1-29.

10. Vidal A, Fallarero A, Pena BR, Medina ME, Gra B, Rivera F, Gutierrez Y, Vuorela PM. 2003. Studies on the toxicity of Punica granatum L. (Punicaceae) whole fruit extracts. J Ethnopharmacol 89:295–300.

11. Larrosa M, Gonzalez-Sarr ´ ´ıas A, Ya´nez-Gasc ˜ on MJ, Selma MV, ´ Azor´ın-Ortuno M, Toti S, Tom ˜ as-Barber ´ an F, Dolara P, Espina JC. 2010. ´ Anti-inflammatory properties of a pomegranate extract and its metabolite urolithin-A. J Nut Biochem 21(8):717–25.

12. Mart´ınez JJ, Melgarejo P, Hernandez F, Salazar DM, Mart’ R. 2006. Seed characterisation of five new pomegranate (Punica granatum L.) varieties. Sci Hortic 110:241–6.

13. Prakash CV, Prakash I. Bioactive chemical constituents from pomegranate (Punica granatum) juice, seed and peel-a review. International Journal of Research in Chemistry and Environment. 2011 Jul;1(1):1-8.

14. Melgarejo P, Salazar DM, Artes F. Organic acids and sugars composition of harvested pomegranate fruits. European Food Research and Technology. 2000 Aug; 211:185-90.

15. Koleckar V, Kubikova K, Rehakova Z, Kuca K, Jun D, Jahodar L, Opletal L. Condensed and hydrolysable tannins as antioxidants influencing the health. Mini reviews in medicinal chemistry. 2008 May 1;8(5):436-47.

16. Kýralan M, Gölükcü M, Tokgöz H. Oil and conjugated linolenic acid contents of seeds from important pomegranate cultivars (Punica granatum L.) grown in Turkey. Journal of the American Oil Chemists' Society. 2009 Oct;86(10):985-90.

17. Lansky EP, Newman RA. Punica granatum (pomegranate) and its potential for prevention and treatment of inflammation and cancer. Journal of ethnopharmacology. 2007 Jan 19;109(2):177-206.

18. Pande G, Akoh CC. Pomegranate cultivars (Punica granatum L.). InNutritional composition of fruit cultivars 2016 Jan 1 (pp. 667-689). Academic Press.

19. Elfalleh W, Tlili N, Ying M, Sheng-Hua H, Ferchichi A, Nasri N. Organoleptic quality, minerals, proteins and amino acids from two Tunisian commercial pomegranate fruits. International Journal of Food Engineering. 2011 Aug 5;7(4).

20. Evtyugin DD, Magina S, Evtuguin DV. Recent advances in the production and applications of ellagic acid and its derivatives. A review. Molecules. 2020 Jun 13;25(12):2745.

21. Singh B, Singh JP, Kaur A, Singh N. Phenolic compounds as beneficial phytochemicals in pomegranate (Punica granatum L.) peel: A review. Food chemistry. 2018 Sep 30; 261:75-86.

22. Borochov-Neori H, Judeinstein S, Harari M, Bar-Ya’akov I, Patil BS, Lurie S, Holland D. Climate effects on anthocyanin accumulation and composition in the pomegranate (Punica granatum L.) fruit arils. Journal of Agricultural and Food Chemistry. 2011 May 25;59(10):5325-34.

23. Sultana B, Anwar F. Flavonols (kaempeferol, quercetin, myricetin) contents of selected fruits, vegetables and medicinal plants. Food chemistry. 2008 Jun 1;108(3):879-84.

24. Ding W, Wang H, Zhou Q, Wu C, Gao X, Cheng X, Tian L, Wang C. Simultaneous determination of polyphenols and triterpenes in pomegranate peel based on HPLC fingerprint by solvent extraction and ratio blending method in tandem with wavelength switching. Biomedical Chromatography. 2019 Dec;33(12):e4690.

25. Poyrazoğlu E, Gökmen V, Artιk N. Organic acids and phenolic compounds in pomegranates (Punica granatum L.) grown in Turkey. Journal of food composition and analysis. 2002 Oct 1;15(5):567-75.

26. Rahmani AH. Cassia fistula Linn: Potential candidate in the health management. Pharmacognosy research. 2015;7(3):217.

27. Rahmani AH, Albutti AS, Aly SM. Therapeutics role of olive fruits/oil in the prevention of diseases via modulation of anti-oxidant, anti-tumour and genetic activity. International journal of clinical and experimental medicine. 2014; 7(4):799-808.

28. Rahmani AH, Aldebasi YH. Potential role of carica papaya and their active constituents in the prevention and treatment of diseases. Int J Pharm Pharm Sci.2016; 8:11-15.

Received on 27.10.2024 Revised on 26.01.2025

Accepted on 18.04.2025 Published on 10.05.2025

Available online from May 14, 2025

Res. J. Pharmacognosy and Phytochem. 2025; 17(2):185-189.

DOI: 10.52711/0975-4385.2025.00030

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.